Research spanning the last decade has significantly elucidated the molecular events attending cell-cell interactions in the body, especially those events involved in the movement and activation of cells in the immune system. See generally, Springer et al., Nature 346:425-434, 1990. Cell surface proteins, and especially the so-called cellular Adhesion Molecules (“CAMs”) have correspondingly been the subject of pharmaceutical research and development having as its goal intervening in the processes of leukocyte extravasation to sites of inflammation and leukocyte movement to distinct target tissues. The isolation and characterization of cellular adhesion molecules, the cloning and expression of DNA sequences encoding such molecules, and the development of therapeutic and diagnostic agents relevant to inflammatory process, viral infection and cancer metastasis have also been the subject of numerous U.S. and foreign applications for Letters Patent. See Edwards, Current Opinion in Therapeutic Patents 1(11):1617-1630, 1991 and particularly the published “patent literature references” cited therein.
Numerous CAMs have been characterized to date. See, for example, vascular adhesion molecule (VCAM-1) as described in PCT WO 90/13300; platelet endothelial cell adhesion molecule (PECAM-1) described in Newman et al., Science 247:1219-1222, 1990; and PCT WO 91/10683; and the following U.S. Pat. Nos.: 5,525,487; 5,235,049; 5,272,263; 5,489,233; 5,264,554; 5,318,890; 5,389,520; 5,519,008; and the like.
There is substantial evidence that N-CAM and its relatives play an important part in neural development (Edelman and Crossin, “CELL ADHESION MOLECULES: Implications for a Molecular Histology”, Ann. Rev. Biochem. 60:155-190, 1991; and Walsh and Doherty, Curr. Opinion in Cell Biol. 5:791-796, 1993). For example, antibodies directed against N-CAMs disturbed the normal growth pattern of nerve processes. N-CAM (locus 11q23.1) is expressed in large amounts in cells of the developing neural tube, but when neural crest cells dissociate from the neural tube and migrate away, they lose N-CAM, only to reexpress it later when they reaggregate to form a neural ganglion. In addition, Rosenthal et al., (Nature Genet. 2:107-112, 1992) reported that mutations in CAM-L1 (locus Xq28) cause X-linked hydrocephalus, and Jouet et al., (Nature Genet. 7:402-407, 1994) showed that mutations in CAM L1 gene are responsible for type 1 X-linked spastic paraplegia and MASA syndrome which shows agenesis of the corpus callosum. Therefore, there is a need in the art to identify and isolate novel N-CAM members of the immunoglobulin superfamily so that their role in neural development and neural cell communication can be determined.
Therefore, there continues to be a need in the art for the discovery of additional proteins participating in human cell-cell interactions and especially a need for information serving to specifically identify and characterize such proteins in terms of their amino acid sequence. Moreover, to the extent that such molecules might form the basis for the development of therapeutic and diagnostic agents, it is essential that the DNA encoding them be elucidated. The present invention satisfies this need and provides related advantages as well.